Numerous studies have shown alcohol and nicotine use are correlated. Further, it has also been shown that smoking is a strong predictor for transitioning from social to problem drinking in adolescents. The reasons why alcohol and nicotine are commonly used together, however, are not completely understood and may involve multiple factors. It is possible that the co-use of alcohol with nicotine may be appealing because nicotine use during alcohol consumption may decrease some of the negative effects of alcohol such as disrupted cognition. The hippocampus is one structure involved in learning that seems particularly sensitive to the disruptive effects of ethanol. For instance, learning the context of an event, a task that is dependent on the hippocampus, is disrupted by ethanol administration in rats and mice. Preliminary findings, however, suggest that nicotine can reverse this deficit. Thus, this ability of nicotine to reduce negative effects of ethanol could facilitate greater or repeated alcohol consumption. This could facilitate a transition in drinking patterns. In addition, repeated nicotine use could also lead to nicotine addiction. It is a hypothesis of this proposal that nicotine will prevent ethanol-induced deficits in contextual conditioning in C57BL/6 mice and that the hippocampus is a neural site were nicotine works to reduce ethanol-associated learning deficits by altering the cellular processes disrupted by ethanol. As an initial step in investigating the interactive effects of nicotine on alcohol use, this proposal will examine the effects of ethanol and nicotine co-administration on hippocampus-dependent learning and also examine the neurobiology that supports ethanol-nicotine interaction. Understanding why nicotine and ethanol are co-used will aid in understanding factors that influence shifts in drinking patterns and nicotine use. Understanding the underlying neurobiology will not only further aid in this understanding but will also aid in developing treatments for alcoholism and nicotine addiction. [unreadable] [unreadable]